This application is a component of an investigator-initiated Interactive Research Project Grant (IRPG) program whose overall objective is to identify and characterize central neurotransmitter systems mediating secretion of oxytocin (OT) in the lactating rat. This component will investigate regulation of norepinephrine (NE) and OT release within hypothalamic nuclei induced by suckling. Previous studies have suggested the importance of intranuclear release of NE and OT in the anterior commissural/paraventricular nucleus area (ACN/PVN), supraoptic nucleus (SON) and the bed nucleus of the stria terminalis (BNST) in systemic OT secretion. However, the stimuli for release and physiological roles of hypothalamic NE and OT in suckling-induced OT secretion are not known. For example, the specific role of somatic stimulation in suckling-induced NE and OT release within hypothalamic nuclei has not been investigated. Furthermore, the importance of intranuclear OT release on systemic OT secretion, and the role of NE in intranuclear OT release are unknown. Finally, the importance of neuromodulators, e.g. histamine (His), angiotensin II (AngII), and glutamate (GLU), which alter CNS NE release, to suckling-induced OT secretion has not been studied. The major objectives of this project are: l) to determine the importance of NE and OT release in the ACN/PVN, SON, and BNST in systemic OT secretion induced by suckling, and 2) to determine if neuromodulators alter intranuclear NE and/or OT secretion evoked by suckling. This project will test the overall hypotheses that l) suckling stimulates NE release in the ACN/PVN, SON and BNST which induces intranuclear OT release and peripheral OT secretion during suckling; and 2) the effects of hypothalamic NE are modulated by His, AngII and GLU. The Specific Aims are: l) measure NE release in the magnocellular nuclei and BNST during suckling and mammary nerve stimulation, 2) determine if central His and/or AngII effect OT secretion by modulating NE release during lactation, and 3) determine neurochemical and neuroendocrine control of intranuclear OT release in the ACN/PVN and SON. These specific aims will be achieved by continuously monitoring extracellular concentrations of neurochemicals in selected brain areas before, during, and following suckling in conscious, unrestrained, lactating rats within vivo microdialysis. Dialysate neurochemicals will be measured with radioimmuno- (OT) and radioenzymatic (NE, His) assays. Furthermore, pharmacological agonists and antagonists will be used to test roles of central neurochemicals (NE, OT) and neuromodulators His, AngII, OLU) on peripheral OT secretion induced by suckling. These studies will contribute to the overall objective of the IRPG by defining the physiological and neurochemical factors that control release of central NE and OT and systemic OT during suckling.